A case of atypical reninoma with mild hypertension and normal plasma renin activity but elevated plasma renin concentration.

BACKGROUND: Reninoma is a rare, benign renal neoplasm. Typical clinical features include severe hypertension, secondary hyperaldosteronism, hypokalaemia and metabolic alkalosis caused by the overproduction of renin. CASE PRESENTATION: A 25-year-old lean Chinese woman with no family history of hypertension was hospitalized for stage 1 hypertension that gradually developed over two years. Endocrine investigation showed hyperreninemia without hyperaldosteronism and hypokalaemia. Interestingly, although the patient had an elevated plasma renin concentration (PRC), her plasma renin activity (PRA) was in the normal range. Abdominal contrast-enhanced computed tomography (CT) scanning revealed a solid, low-density, renal cortical mass with delayed enhancement. Selective renal vein sampling (SRVS) was performed, and a lateralization of the renin secretion from the left kidney was found. Enucleation of the tumour led to a rapid remission of hypertension and hyperreninemia. Based on pathological findings, the patient was diagnosed with reninoma. Immunohistochemical staining of the tumour was positive for Renin, CD34, Vimentin, and synaptophysin (Syn) and negative for somatostatin receptor 2 (SSTR2) and chromogranin A (CgA). CONCLUSIONS: Reninoma can present as mild hypertension without hyperaldosteronism and hypokalaemia. The clinical features of reninoma may depend on the degree of activation of the renin-angiotensin-aldosterone system (RAAS). PRC should be incorporated in the differential diagnosis of secondary hypertension.

High DND1 Level Indicates a Poor Prognostic Factor in Prostate Cancer.

BACKGROUND: Dead end 1 (DND1) plays a vital role during oncogenesis and cancer progression by regulating the mRNA content via competitive combination with miRNA, but what function it exerts in prostate cancer has been unclear. The purpose of this paper is to explore the correlation between DND1 expression levels and clinical characteristics in prostate cancer (PCa) patients. MATERIALS AND METHODS: To assess the expression of DND1 in tumor specimens compared with paired paracancerous tissues, the sample from 83 patients was analyzed by immunohistochemistry. The Cancer Genome Atlas (TCGA) database was used to verify our results. Subsequently, we statistically analyzed the relationship between DND1 expression and the clinical prognosis of PCa patients. RESULTS: Compared with paracancerous tissues, DND1 has a higher expression level in prostate cancer. The overexpression of DND1 in protein level was significantly associated with the higher clinical stage (P = 0.006), ISUP grading group (P < 0.001), seminal vesicle invasion (P = 0.006), and PSA density (P = 0.002). Furthermore, the overexpression of DND1 indicates a poor clinical prognosis in prostate cancer patients. CONCLUSION: High-level expression of DND1 was associated with tumor progression and poor clinical prognosis. Hence, DND1 may become a potential prognostic biomarker for PCa.

ABT­737, a Bcl­2 family inhibitor, has a synergistic effect with apoptosis by inducing urothelial carcinoma cell necroptosis.

ABT­737 is a recently reported inhibitor of members of the Bcl­2 family of apoptosis regulators. However, to the best of our knowledge, its necroptosis­inducing function in bladder cancer has not yet been researched. Thus, the present study aimed to investigate whether this Bcl­2 family inhibitor can induce both apoptosis and necroptosis of urothelial carcinoma cells. The proliferation and survival of urothelial carcinoma cell lines treated with a combination of both Z­VAD­FMK as a pan­caspase inhibitor and ABT­737 were assessed in vitro. Z­DNA binding protein 1 (ZBP1), receptor­interacting protein (RIP)1 and RIP3 were knocked down using small interfering RNA in urothelial carcinoma cell lines. The protein expression levels of ZBP1, RIP1 and RIP3 following cell transfection were measured via western blot analysis. Cell viability was determined using an MTT assay. Cell invasion was examined using cell invasion assays. The expression levels of necroptosis­related proteins, high mobility group box 1, ZBP1, mixed­lineage kinase domain­like protein (MLKL) and RIP3, were measured via western blotting. It was found that ABT­737 inhibited the proliferation and invasion of bladder cancer cells by inducing cell necrosis. The data demonstrated that ZBP1 and RIP3 have main roles in the cell necrosis induced by ABT­737. In addition, RIP3 and ZBP1, without interacting with RIP1, directly induced MLKL­mediated programmed cell necrosis. Thus, understanding how urothelial carcinoma cells react to Bcl­2 family inhibitors may accelerate the discovery of drugs to treat bladder cancer.

Lipidomics reveal aryl hydrocarbon receptor (Ahr)-regulated lipid metabolic pathway in alpha-naphthyl isothiocyanate (ANIT)-induced intrahepatic cholestasis.

1. Ultra-performance liquid chromatography coupled with electrospray ionization quadrupole mass spectrometry (UPLC-ESI-QTOF MS)-based lipidomics was employed to elucidate new mechanism of alpha-naphthyl isothiocyanate (ANIT)-induced intrahepatic cholestasis in mice. 2. Multiple lipid components significantly increased in ANIT-induced intrahepatic cholestasis, including PC 16:0, 20:4, PC 16:0, 22:6, PC 16:0, 18:2, LPC 18:2, PC 18:2, LPC 18:1, PC 18:1, 14:0, SM 18:1, 16:0, oleoylcarnitine and palmitoylcarnitine. This alteration of lipid profile was induced by the changed expression of genes choline kinase (Chk) a, sphingomyelin phosphodiesterase (SMPD) and stearoyl-coenzyme A desaturase 1 (SCD1). 3. Knockout of aryl hydrocarbon receptor (Ahr) in mice can significantly reverse ANIT-induced intrahepatic cholestasis, as indicated by lowered ALT, AST and ALP activity, and liver histology. Aryl hydrocarbon receptor knockout significantly reversed ANIT-induced lipid metabolism alteration through regulating the expression of Chka. 4. In conclusion, this study demonstrated ANIT-induced lipid metabolism disruption might be the potential pathogenesis of ANIT-induced intrahepatic cholestasis in mice.

Comparison of hydrocortisone and prednisone in the glucocorticoid replacement therapy post-adrenalectomy of Cushing's Syndrome.

Cushing's syndrome requires glucocorticoid replacement following adrenalectomy. Based on a simplified glucocorticoid therapy scheme and the peri-operative observation, we investigated its efficacy and safety up to 6 months post-adrenalectomy in this cohort study. We found the adrenocorticotropic hormone (ACTH) levels were normal post-adrenalectomy, and sufficient to stimulate the recovery of the dystrophic adrenal cortex, thus exogenous supplemental ACTH might not be necessary. Patients were grouped by oral reception of either hydrocortisone or prednisone since day 2 post-adrenalectomy. Both groups had similar baseline responses to adrenalectomy, regarding the correction of hypertension (10/15 vs.12/19), hyperglycemia (6/11 vs. 7/10), and hypokalemia (12/12 vs. 11/11). Most patients lost weight (17/20 vs. 20/22). Both groups reported significant improvement in a subjective evaluation questionnaire. Hydrocortisone showed advantages over prednisone in improving liver function (7/8 vs. 2/7, p = 0.035), but also caused significant lower extremety edema (p = 0.034). Both groups developed adrenal insufficiency (AI) during glucocorticoid withdrawal, with no significant difference regarding the incidence rate (7/20 vs. 10/22) or severity. Most AI symptoms were relieved by resuming the prior oral doses, while two severe cases were hospitalized. The withdrawal process may last longer time for hydrocortisone than prednisone. In conclusion, our data supports the use of both hydrocortisone and prednisone in the glucocorticoid replacement therapy post-adrenalectomy for patients of adrenal adenoma or Cushing's disease. Hydrocortisone showed advantages over prednisone in improving liver function, and prednisone exhibited significantly lower risk of edema.

Diagnosis and surgical treatment of multiple endocrine neoplasia type 2A.

BACKGROUND: This study aims to introduce the diagnosis and surgical treatment of the rare disease multiple endocrine neoplasia type 2A (MEN 2A). METHODS: Thirteen cases of MEN 2A were diagnosed as medullary thyroid carcinoma (MTC) and pheochromocytoma by biochemical tests and imaging examination. They were treated by bilateral adrenal tumor excision or laparoscopic surgery. RESULTS: Nine patients were treated by bilateral adrenal tumor excision and the remaining four were treated by laparoscopic surgery for pheochromocytoma. Ten patients were treated by total thyroidectomy and bilateral lymph nodes dissection and the remaining three were treated by unilateral thyroidectomy for MTC. Up to now, three patients have died of MTC distant metastasis. CONCLUSIONS: We confirmed that MEN 2A can be diagnosed by biochemical tests and imaging examination when genetic testing is not available. Surgical excision is the predominant way to treat MEN 2A; pheochromocytoma should be excised at first when pheochromocytoma and MTC occur simultaneously.

Sexual function improvement in association with serum leptin level elevation in patients with premature ejaculation following sertraline treatment: a preliminary observation.

The objective of our work was to evaluate the effect of sertraline hydrochloride on serum levels of leptin and sexual function in patients with premature ejaculation (PE). A total of 124 patients with a history of PE at least 6 months, aged 20-50 years, were treated with sertraline hydrochloride. One hundred and four age-matched normal males without a history of PE were included control subjects and were untreated. Before and after the 8 week experiment, sexual performance parameters including the intravaginal ejaculation latency time (IELT) and the Chinese premature ejaculation index (CIPE) were collected from both PE patients and control subjects through a questionnaire survey and analyzed. Serum levels of leptin were measured. Correlations of serum leptin with Body Mass Index (BMI) were analyzed. Before sertraline treatment, serum levels of leptin were significantly higher (32.9 vs 8.8 µg/L, p<0.001) but IELT and CIPE score were significantly lower (54 vs 590, p <0.001; 8.7 vs 22.3, p <0.0001) in PE patients than control subjects. After 8 weeks of treatment with sertraline, serum levels of leptinl in PE patients were decreased markedly to 8.0 µg/L, which was not significantly different from the levels in control subjects (p >0.05); and IELT and CIPE score in PE patients were increased to the values similar to those in control subjects. The sensitivity and specificity values were 87.5% and 96.3% for leptin as a diagnosis target. These observations suggest sertraline as a selective serotonin reuptake inhibitor may offer an effective option for treating premature ejaculation.

Serum leptin and 5-hydroxytryptamine measurements for the diagnosis and treatment of premature ejaculation.

OBJECTIVE: To study the significance of measurements of plasma leptin and 5-hydroxytryptamine (5-HT) levels in the diagnosis of premature ejaculation (PE). METHODS: We compared plasma leptin and 5-HT levels, intravaginal ejaculation latency time (IELT) and Chinese Index of Premature Ejaculation-5 (CIPE-5) scores between 59 patients with PE and 64 healthy control men without PE. We then analyzed the correlations of plasma leptin and 5-HT levels with the IELT and CIPE-5 scores. The patients with PE were administered sertraline (50mg daily) for 8 weeks, and their plasma leptin and 5-HT levels, CIPE-5 scores and IELT were measured again. Comparative analyses of the data were performed between the experimental and control groups and between the pre- and post-treatment values. RESULTS: Plasma leptin levels were significantly higher (P <.0001), whereas plasma 5-HT levels (P <.0001), IELT (P <.0001), and CIPE-5 scores (P <.0001) were significantly lower in the experimental group than in the control group. Significant changes in leptin and 5-HT levels, IELT and CIPE-5 scores were observed after treatment in the experimental group. Plasma leptin levels negatively correlated with 5-HT levels, CIPE-5 scores, and IELT, whereas 5-HT levels positively correlated with IELT and CIPE-5 scores. CONCLUSION: Plasma leptin and 5-HT levels indicate the presence of PE and can be used as diagnostic markers for PE.

Clinical value of serum 5-HT level in diagnosis and treatment of premature ejaculation.

OBJECTIVE: To investigate serum 5-HT level in premature ejaculation (PE) patients and evaluate its clinical value in diagnosis and treatment of PE. METHODS: 71 patients were recruited in this study. Their serums were collected before and after sertraline treatment, while serums from 64 normal males were also collected as a control. Serum 5-HT level was detected by ELISA. SPSS 17.0 software was used to analyze the level of serum 5-HT and the ROC curve was drawn. RESULTS: The average serum 5-HT level of PE patients was 61.9 ng/ml in our study, which was significantly lower than that of the control group (120.6 ng/ml), with statistical significance (p < 0.01). After sertraline treatment, the average serum 5-HT level in PE patients was 98.9 ng/ml, which was significantly higher than that before sertraline treatment. Sensitivity and specificity for serum 5-HT as a predictive diagnostic tool for PE were 92.2 and 93.0%, respectively, and the cutoff value of serum 5-HT was 86.4 ng/ml. CONCLUSIONS: Our study showed that serum 5-HT level may be used as a functional diagnostic tool for PE and an indicator in PE treatment.